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Biological, Immunological, and Molecular Properties of Revertants of Cat Cells Transformed by Murine Sarcoma Virus

Laboratories of Viral Carcinogenesis [P. J. F., C. S. B., A. E. F., N. T-F., D. K. H., S. N.] and Molecular Virology [W. G. R.], National Cancer Institute, Bethesda, Maryland 20205

Cloned cat cells (CCC) transformed by the m1 isolate of Moloney murine sarcoma virus (MSV) have the properties of sarcoma-positive, leukemia-negative (S+L-) cells. Over the past 5 years, partially flat as well as very contact-inhibited variant clones were isolated from several clonal generations of S+L- cat cells. Partially flat subclones still contained the MSV genome and could serve as useful cell systems for quantal assays for a number of replicating retroviruses. The frequency of isolation of rescue-negative, very flat subclones diminished with sequential cloning cycles of S+L- cells. The rescuenegative revertant cells grew to low density in liquid media, were more similar to normal cells in soft-agar colony formation, and were intermediate in concanavalin A agglutinability when compared to normal or S+L- cells. Revertants could be retransformed by pseudotypes of MSV other than MSV coated with feline endogenous xenotropic virus. Feline endogenous xenotropic virus was readily induced from S+L- cells but was not inducible from some revertants by halogenated pyrimidines. Rescue-negative revertants could support the growth of a number of helper viruses. Chromosomes of parental CCC normal cells, MSV producer cells, S+L- cells, or revertants were all significantly hypodiploid. No stable pathognomonic changes were observed relative to type and chromosome number among the above. The MSV-coded precursor polyprotein with a molecular weight of 60,000 was detected in producer and S+L- cells but not detected in revertants. Producer and S+L- cells had multiple MSV src copies in their DNA, whereas revertants did not contain residual src DNA. The number of either feline endogenous xenotropic virus or feline leukemia virus-like DNA copies was not different among producer, S+L-, or revertant cells. Accordingly, all rescue-negative cat cell revertants tested have lost multiple copies of MSV proviral DNA.

¹ Present address: Virus Control Section, National Cancer Institute, Frederick Cancer Research Center, Frederick, Md. 21701. To whom requests for reprints should be addressed.

Received 8/ 1/80. Accepted 11/14/80.